Important morphological and biochemical changes occur during differentiation in African trypanosomes. This proposal seeks to identify the molecular basis of differentiation as bloodstream trypomastigotes differentiate to procyclic trypomastigotes. We shall be particularly interested in the following related areas of research: 1. Investigate the expression of nuclear and mitochondrial genes essential during differentiation in African trypanosomes using cloned trypanosome genes for apocytochrome b and apocytochrome c, identifying transcripts for these genes. 2. Determine what factors or conditions stimulate and influence synthesis of the mitochondrial electron transport system during differentiation. We shall examine particularly the role of heme, oxygen, glucose and cis-aconitate. 3. Further purify the alpha glycerophosphate oxidase (Alpha-GP oxidase). The solubilized ubiquinol oxidase activity will be utilized in order to characterize this important oxidase. We consider the role of the nuclear and mitochondrial DNA importance in the biosynthesis of the mitochondrial electron transport system. More research at the molecular level on the factors which influence transcription of nuclear and mitochondrial genes during differentiation in this system will provide clues to the regulation of the life cycle of these organisms which could be important with regard to control of this important parasite. In addition, important factors may be revealed which elucidate the basis for parasitism in this host-parasite relationship.